Famciclovir (9-[4-acetoxy-3-(acetoxymethyl)but-1-yl]-2-aminopurin) is one of a number of compounds known to have useful antiviral activity and described, for example, in EP 141,927. Famciclovir has antiviral activity relevant for treatment of a number of viral infections, including herpes simplex, varicella-zoster and hepatitis.
A number of different routes for preparation of purine derivatives such as famciclovir are known, including those described in EP 182,024, EP 141,927, EP 352,953, U.S. Pat. No. 5,684,153, U.S. Pat. No. 5,138,057, U.S. Pat. No. 5,917,041, U.S. Pat. No. 6,761,767, Geen et al. (2001) in Tet. Lett. 42(9) 1781, Harnden et al. (1989) in J. Med. Chem. 32(8) 1738, Hamden et al. (1990) in Nucleosides and Nucleotides 9(4) 499, Izawa and Shiragami (1998) in Pure and Applied Chemistry 70(2) 313 and WO 2004/110343.
One method, set out below in Scheme 1, is known from EP 182,024 and U.S. Pat. Nos. 5,684,153; 5,138,057 and 6,761,767. Here the X on starting compound 6 is either halogen or any other leaving group such as tosyl or mesyl.

The starting material, 2-amino-6-chloro-purine (compound 1), is commercially available at a reasonable price. However, a common problem associated with this process is lack of regioselectivity as the undesired 7-position isomer is generated simultaneously, reducing yield and requiring a separation step to remove this unwanted (inactive) isomer.
A further method, set out as Scheme 2, is known from U.S. Pat. No. 5,971,041.

The method of Scheme 2 tries to address this problem in order to maximize the percentage of desired 9-substituted compound by carefully controlling the reaction conditions. However, starting compounds 8 and 9 are not commercially available and have to be prepared separately. Also, the overall yield for famciclovir is low, less than 30%.
A more recent method, set out as Scheme 3, is described in WO 2004/110343.
But this process only produce famciclovir at about 18% overall yield. Again, compound 11 used in this process is not commercially available and has to be prepared from nitrouracil.
The methods described in scheme 2 and 3 provide a solution to the above mentioned regioselectivity problem by introducing the alkyl side-chain first onto the desired 9-position before the formation of fused imidazole ring. Nevertheless, a common drawback in these methods is their lengthy procedure and overall low yield.
An object of the present invention is to provide an alternative process for preparation of purine derivatives such as famciclovir.
An object of specific embodiments of the invention is to provide a process for preparation of these purine derivatives with improved efficiency, for example with a reduced number of steps and/or improved yield of the desired end product.